Tereza Halkova1,2, Sarka Dvorakova1, Vlasta Sykorova1, Eliska Vaclavikova1, Josef Vcelak1, Petr Vlcek3, Pavla Sykorova3, Daniela Kodetova4, Jan Betka5, Petr Lastuvka5, Petr Bavor6, Jiri Hoch6, Rami Katra7, Bela Bendlova1. 1. Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic. 2. Department of Biochemistry, Faculty of Science, Charles University in Prague, Prague, Czech Republic. 3. Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic. 4. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic. 5. Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic. 6. Department of Surgery, 2nd Faculty of Medicine, Charles University and Faculty Hospital Motol, Prague, Czech Republic. 7. Department of ENT, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
Abstract
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS: XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.
BACKGROUND:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTCpatients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS:XRCC1T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.
Authors: Fanny Chasseloup; Nathan Pankratz; John Lane; Fabio R Faucz; Margaret F Keil; Prashant Chittiboina; Denise M Kay; Tara Hussein Tayeb; Constantine A Stratakis; James L Mills; Laura C Hernández-Ramírez Journal: J Clin Endocrinol Metab Date: 2020-06-01 Impact factor: 5.958